Prostaglandins appear to be local regulatory substances in gastrointestinal muscles. Experiments reported previously have shown that the "prostaglandin effect" in circular muscles of the gastric antrum and small bowel is inhibitory, i.e. decreasing tissue concentrations of prostaglandins in these tissues increased the amplitude of electrical slow waves and the force of contractions. Preliminary experiments have shown that prostaglandins may also regulate the frequency of contractions. Inhibition of prostaglandin synthesis decreased spontaneous frequency and blocked the frequency effect of pentagastrin. Exogenous prostaglandin E2 increased slow wave frequency and the frequency effect of pentagastrin. The main goal of this grant is to investigate the role of prostaglandins in regulating the frequency of slow waves in corpus and antral muscles of the canine stomach. As a consequence of these studies important information about the physiological mechanisms regulating slow wave frequency will be obtained. The frequency of slow waves determines the site of slow wave origin in the stomach. Normally the frequency is highest in the orad corpus, so this region of the musculature serves as the gastric "pacemaker". The slow waves propagate in 3 dimensions from the site of origin, determining the pattern of the contractile wave. If conditions exist where a high frequency pacemaker develops in another region of the stomach, abnormal patterns of propagation can result and cause abnormal motility. Prostaglandins have been implicated in at least one case of "gastric arrhythmia" in which antral frequency was elevated causing chronic gastric retention. This project will evaluate the effects of prostaglandins of slow wave frequency, and with a precise new technique, determine whether prostaglandins can alter the pattern of slow wave propagation in gastric muscles.